Esculetin derivatives and pharmaceutical composition

Abstract

A pharmaceutical composition comprising a compound of the general formula (I): ##STR1## wherein R 1 and R 2 are, independently, a hydrogen atom, a saturated or unsaturated aliphatic acyl having 2 to 25 carbon atoms or benzoyl group and R 3 is a hydrogen atom or alkyl group, and a pharmaceutically acceptable carrier is disclosed. Further, a novel compound of the general formula (I) wherein R 1 and R 2 are, independently, a hydrogen atom, pivaloyl, capryloyl, lauroyl, palmitoyl, stearoyl, linoleoyl, docosahexaenoyl, or benzoyl group, and R 3 is a hydrogen atom or methyl group, is also disclosed.

I claim: 
     
       1. A pharmaceutical composition, comprising a compound of the formula (I): ##STR4## wherein R 1  and R 2  are, independently, a hydrogen atom, a saturated or unsaturated aliphatic acyl having 2 to 25 carbon atoms or a benzoyl group, and R 3  is a hydrogen atom or an alkyl group, and a pharmaceutically acceptable carrier, with the proviso that when R 3  is a hydrogen atom, R 1  and R 2  are not hydrogen atoms or acetyl groups at the same time, or when R 3  is a methyl group, R 1  and R 2  are not hydrogen atoms, acetyl groups, palmitoyl groups, capryloyl groups or lauroyl groups at the same time. 
     
     
       2. A pharmaceutical composition according to claim 1, wherein R 1  and R 2  are, independently, a hydrogen atom, an acetyl group, a pivaloyl group, a capryloyl group, a lauroyl group, a palmitoyl group, a stearoyl group, a linoleoyl group, a docosahexaenoyl group, or a benzoyl group, and R 3  is a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. 
     
     
       3. A pharmaceutical composition according to claim 2, wherein R 1  and R 2  are, independently, a hydrogen atom, a pivaloyl group, a capryloyl group, a lauroyl group, a palmitoyl group, a stearoyl group, a linoleoyl group, a docosahexaenoyl group, or a benzoyl group, and R 3  is a hydrogen atom or a methyl group. 
     
     
       4. A pharmaceutical composition according to claim 3, wherein R 1  and R 2  are, independently, a hydrogen atom, a pivaloyl group, a stearoyl group, or a benzoyl group. 
     
     
       5. A method for treating arthropathy, comprising administering to a mammal in need thereof an arthropathy treating effective amount of a compound of the formula (I): ##STR5## wherein R 1  and R 2  are, independently, a hydrogen atom, a saturated or unsaturated aliphatic acyl having 2 to 25 carbon atoms or a benzoyl group, and R 3  is a hydrogen atom or an alkyl group. 
     
     
       6. A method for treating arthropathy according to claim 5, wherein R 1  and R 2  are independently, a hydrogen atom, an acetyl group, a pivaloyl group, a capryloyl group, a lauroyl group, a palmitoyl group, a stearoyl group, a linoleoyl group, a docosahexaenoyl group, or a benzoyl group, and R 3  is a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. 
     
     
       7. A method for treating arthropathy according to claim 6, wherein R 1  and R 2  are, independently, a hydrogen atom, a pivaloyl group, a capryloyl group, a lauroyl group, a palmitolyl group, a stearoyl group, a linoleoyl group, a docasahexaenoyl group, or a benzoyl group, and R 3  is a hydrogen atom or a methyl group. 
     
     
       8. A method for treating arthropathy according to claim 7, wherein R 1  and R 2  are, independently, a hydrogen atom, a pivaloyl group, a stearoyl group or a benzoyl group. 
     
     
       9. A method for treating arthropathy according to claim 5, wherein the compound is selected from the group consisting of esculetin, 4-methylesculetin, esculetin 6,7-bis(acetate), 4-methylesculetin 6,7-bis(acetate), esculetin 6,7-bis(pivalate), 4-methylesculetin 6,7-bis(pivalate), esculetin 6-monopivalate, 4-methylesculetin 6-monopivalate, esculetin 7-monopivalate, 4-methylesculetin 7-monopivalate, esculetin 6,7-bis(caprylate), 4-methylesculetin 6,7-bis(caprylate), esculetin 6,7-bis(laurate), 4-methylesculetin 6,7-bis(laurate), esculetin 6,7-bis(palmitate), 4-methylesculetin 6,7-bis(palmirate), esculetin 6,7-bis(stearate), 4-methylesculetin 6,7-bis(stearate), esculetin 6,7-bis(linoleate), 4-methylesculetin 6,7-bis(linoleate), esculetin 6,7-bis(docosahexaenoate), 4-methylesculetin 6,7-bis(docosahexaenoate), and esculetin 6,7-bis(benzoate), 4-methylesculetin 6,7-bis(benzoate). 
     
     
       10. A method for treating arthropathy according to claim 9, wherein the compound is selected from the group consisting of esculetin 6-monopivalate, esculetin 6,7-bis(pivalate), esculetin 6,7-bis(stearate), 4-methylesculetin 6,7-bis(stearate), 4-methylesculetin 6,7-bis(linoleate), 4-methylesculetin 6,7-bis(docosahexaenoate) and 4-methylesculetin 6,7-bis(benzoate). 
     
     
       11. A method for protecting cartilage, comprising administering to a mammal in need thereof a cartilage protecting amount of a compound of formula (I): ##STR6## wherein R 1  and R 2  are, independently, a hydrogen atom, a saturated or unsaturated aliphatic acyl having 2 to 25 carbon atoms or a benzoyl group, and R 3  is a hydrogen atom or an alkyl group. 
     
     
       12. A method for protecting cartilage according to claim 11, wherein R 1  and R 2  are independently, a hydrogen atom, an acetyl group, a pivaloyl group, a capryloyl group, a lauroyl group, a palmitoyl group, a stearoyl group, a linoleoyl group, a docosahexaenoyl group, or a benzoyl group, and R 3  is a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. 
     
     
       13. A method for protecting cartilage according to claim 12, wherein R 1  and R 2  are, independently, a hydrogen atom, a pivaloyl group, a capryloyl group, a lauroyl group, a palmitolyl group, a stearoyl group, a linoleoyl group, a docasahexaenoyl group, or a benzoyl group, and R 3  is a hydrogen atom or a methyl group. 
     
     
       14. A method for protecting cartilage according to claim 13, wherein R 1  and R 2  are, independently, a hydrogen atom, a pivaloyl group, a stearoyl group or a benzoyl group. 
     
     
       15. A method for protecting cartilage according to claim 11, wherein the compound is selected from the group consisting of esculetin, 4-methylesculetin, esculetin 6,7-bis(acetate), 4-methylesculetin 6,7-bis(acetate), esculetin 6,7-bis(pivalate), 4-methylesculetin 6,7-bis(pivalate), esculetin 6-monopivalate, 4-methylesculetin 6-monopivalate, esculetin 7-monopivalate, 4-methylesculetin 7-monopivalate, esculetin 6,7-bis(caprylate), 4-methylesculetin 6,7-bis(caprylate), esculetin 6,7-bis(laurate), 4-methylesculetin 6,7-bis(laurate), esculetin 6,7-bis(palmitate), 4-methylesculetin 6,7-bis(palmirate), esculetin 6,7-bis(stearate), 4-methylesculetin 6,7-bis(stearate), esculetin 6,7-bis(linoleate), 4-methylesculetin 6,7-bis(linoleate), esculetin 6,7-bis(docosahexaenoate), 4-methylesculetin 6,7-bis(docosahexaenoate), and esculetin 6,7-bis(benzoate), 4-methylesculetin 6,7-bis(benzoate). 
     
     
       16. A method for protecting cartilage according to claim 15, wherein the compound is selected from the group consisting of esculetin 6-monopivalate, esculetin 6,7-bis(pivalate), esculetin 6,7-bis(stearate), 4-methylesculetin 6,7-bis(stearate), 4-methylesculetin 6,7-bis(linoleate), 4-methylesculet in 6,7-bis(docosahexaenoate) and 4-methylesculetin 6,7-bis(benzoate).